The Pit-1 homeodomain and beta-domain interact with Ets-1 and modulate synergistic activation of the rat prolactin promoter.
J Biol Chem
; 275(5): 3100-6, 2000 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-10652292
ABSTRACT
Pit-1/GHF-1 is a pituitary-specific, POU homeodomain transcription factor required for development of somatotroph, lactotroph, and thyrotroph cell lineages and regulation of the temporal and spatial expression of the growth hormone, prolactin (PRL), and thyrotropin-beta genes. Synergistic interaction of Pit-1 with a member of the Ets family of transcription factors, Ets-1, has been shown to be an important mechanism regulating basal and Ras-induced lactotroph-specific rat (r) PRL promoter activity. Pit-1beta/GHF-2, an alternatively spliced isoform containing a 26-amino acid insert (beta-domain) within its transcription-activation domain, physically interacts with Ets-1 but fails to synergize. By using a series of Pit-1 internal-deletion constructs in a transient transfection protocol to reconstitute rPRL promoter activity in HeLa cells, we have determined that the functional and physical interaction of Pit-1 and Ets-1 is mediated via the POU homeodomain, which is common to both Pit-1 and Pit-1beta. Although the Pit-1 homeodomain is both necessary and sufficient for direct binding to Ets-1 in a DNA-independent manner, an additional interaction surface was mapped to the beta-domain, specific to the Pit-1beta isoform. Thus, the unique transcriptional properties of Pit-1 and Pit-1beta on the rPRL promoter may be due to the formation of functionally distinct complexes of these two Pit-1 isoforms with Ets-1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prolactina
/
Fatores de Transcrição
/
Transdução de Sinais
/
Proteínas Proto-Oncogênicas
/
Regiões Promotoras Genéticas
/
Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos